Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway

Cheng,Xiaoli; Shi,Wenli; Zhao,Canguo; Zhang,Dan; Liang,Piao; Wang,Guohui; Lu,Li

doi:10.3892/mmr.2016.4931

Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway

Authors:
- Xiaoli Cheng
- Wenli Shi
- Canguo Zhao
- Dan Zhang
- Piao Liang
- Guohui Wang
- Li Lu
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Affiliations: Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China, Department of Pathology, Guangzhou Nansha Central Hospital, Guangzhou First Municipal People's Hospital, Guangzhou, Guangdong 510180, P.R. China, Department of Internal Medicine, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China
Published online on: February 23, 2016 https://doi.org/10.3892/mmr.2016.4931
Pages: 3257-3264

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Abstract

Tumor necrosis factor‑α (TNF‑α) can act as either a tumor promoter, linking inflammation with carcinogenesis, or a tumor inhibitor, inducing cancer cell death. However, several types of cancer, including breast cancer, are resistant to TNF‑α therapy. Triptolide, a diterpene triepoxide, has been reported to exert anti‑inflammatory and antiproliferative effects, associated with the inhibition of nuclear factor‑κB (NF‑κB). The present study investigated the effects of triptolide sensitization on human breast cancer cells to TNF‑α‑induced apoptosis by inhibiting activation of the NF‑κB pathway. Human breast cancer MDA‑MB‑231 cells and MCF‑7 cells were treated with different concentrations of triptolide, with or without 10 ng/ml TNF‑α, for different durations, followed by measurement of cell proliferation using a 3‑[4,5‑dimethyltiazol‑2‑yl]‑2.5‑diphenyl‑tetrazolium bromide assay, apoptosis induction, through determination of caspase‑3 activity and poly (ADP‑ribose) polymerase (PARP) cleavage, and NF‑κB pathway activation, through determination of inhibitor of NF‑κB (IκB) and the NF‑κB downstream genes, X‑linked inhibitor of apoptosis protein (XIAP) and cellular inhibitor of apoptosis protein1/2 (cIAP1/2)] using Western blot and reverse transcription‑quantitative polymerase chain reaction analyses. TNF‑α, when combined with triptolide, was observed to inhibit the activation of IκBα, increase the level of cleaved PARP, and further activate caspase‑3 in the breast cancer cells. Triptolide also inhibited the expression levels of the downstream anti‑apoptotic genes of NF‑κB activation, XIAP and cIAP1/2. The results of the present study demonstrated that triptolide sensitized human breast cancer cells to TNF‑α‑induced apoptosis, which may provide a promising combination strategy for human breast cancer therapeutics.

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